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Chemical Structure| 6089-04-9 Chemical Structure| 6089-04-9

Structure of 6089-04-9

Chemical Structure| 6089-04-9

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Product Details of [ 6089-04-9 ]

CAS No. :6089-04-9
Formula : C8H12O2
M.W : 140.18
SMILES Code : C#CCOC1CCCCO1
MDL No. :MFCD00006604
InChI Key :HQAXHIGPGBPPFU-UHFFFAOYSA-N
Pubchem ID :98609

Safety of [ 6089-04-9 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225
Precautionary Statements:P210-P403+P235
Class:3
UN#:1993
Packing Group:

Computational Chemistry of [ 6089-04-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 38.79
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

18.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.26
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.05
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.24
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.16
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.51

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.24
Solubility 8.09 mg/ml ; 0.0577 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.03
Solubility 13.1 mg/ml ; 0.0937 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-0.98
Solubility 14.7 mg/ml ; 0.105 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.41 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

3.6

Application In Synthesis of [ 6089-04-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 6089-04-9 ]

[ 6089-04-9 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 6214-35-3 ]
  • [ 6089-04-9 ]
  • (Z)-5-(2-(tetrahydro-2H-pyran-2-yloxy)ethylidene)furan-2(5H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With copper(l) iodide; palladium 10% on activated carbon; triethylamine; triphenylphosphine; In 1,4-dioxane; at 25 - 80℃; for 3.5h;Inert atmosphere; General procedure: (a) The reaction was performed in a bigger scale using 100 mg of 10% Pd/C (0.092 mmol), PPh3 (0.37 mmol), CuI (0.184 mmol), Et3N (10.68 mmol), compound 1a (3.56 mmol), and acetylenic compound 2a (5.32 mmol) in 1,4-dioxane (20.0 mL). After stirring at 80 C for 3 h under nitrogen the mixture was cooled to room temperature. The Pd/C was filtered off and washed with water (2 10 mL), acetone (2 10 mL), and EtOAc (2 10 mL). Then the catalyst was collected, dried at 100 C in an oven, and reused for the next run. The co-catalyst CuI along with PPh3 was added in every repeated run. (b) General method for the preparation of 3: A mixture of compound 1 (0.89 mmol), 10% Pd/C (0.023 mmol), PPh3 (0.092 mmol), CuI (0.046 mmol), and Et3N (2.67 mmol) in 1,4-dioxane (5.0 mL) was stirred at 25 C for 30 min under nitrogen. The acetylenic compound 2 (1.33 mmol) was added slowly with stirring. The mixture was then stirred at 80 C for 3 h, cooled to room temperature, diluted with EtOAc (30 mL), and filtered through celite. The filtrate was collected and concentrated. The residue was purified by column chromatography (2-15% EtOAc/hexane) to afford the desired product
  • 2
  • [ 53400-41-2 ]
  • [ 6089-04-9 ]
  • [ 1194586-55-4 ]
  • 3
  • [ 6089-04-9 ]
  • [ 201230-82-2 ]
  • [ 302-15-8 ]
  • [ 103962-05-6 ]
  • [ 1202942-19-5 ]
YieldReaction ConditionsOperation in experiment
64% With sodium hydrogencarbonate;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; water; at 20℃; for 48h;Inert atmosphere; M. Synthesis of (6S)-6-({1-methyl-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-5-yl}methoxy)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (11) by the method of Scheme 8 A solution of 2-(2-propynyloxy)tetrahydro-2H-pyran (69) (0.758 g, 5.41 mmol), CuI (17 mg, 0.09 mmol) and PdCl2(PPh3)2 (0.158 g, 0.023 mmol) in THF (15 mL) was purged with N2. 1-Iodo-4-(trifluoromethoxy)benzene (70) (1.30 g, 4.51 mmol) in THF (10 mL) was added, followed by a solution of methylhydrazine sulfate (1.95 g, 13.5 mmol) and NaHCO3 (2.27 g, 27 mmol) in water (25 mL). The mixture was flushed with carbon monoxide and then stirred at room temperature for 2 days under one atmosphere of carbon monoxide. The resulting mixture was partitioned between CH2Cl2 and water, the CH2Cl2 fraction was dried, and the solvent was evaporated. Column chromatography of the residue on silica gel (eluting with CH2Cl2) gave 1-methyl-5-[tetrahydro-2H-pyran-2-yloxy)methyl]-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazole (71) (1.034 g, 64%) as a brown solid: mp 40-42 C.; 1H NMR (CDCl3) δ 7.78 (d, J=8.8 Hz, 2H), 7.21 (d, J=8.0 Hz, 2H), 6.51 (s, 1H), 4.75 (d, J=12.8 Hz, 1H), 4.69 (t, J=3.3 Hz, 1H), 4.57 (d, J=12.8 Hz, 1H), 3.94 (s, 3H), 3.84-3.91 (m, 1H), 3.53-3.60 (m, 1H), 1.68-1.88 (m, 2H), 1.50-1.66 (m, 4H). APCI MS m/z 357 [M+H]+.
  • 4
  • [ 914347-21-0 ]
  • [ 6089-04-9 ]
  • [ 1231952-94-5 ]
YieldReaction ConditionsOperation in experiment
88% With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; at 100.0℃; for 0.5h;Inert atmosphere; Microwave irradiation; Nitrogen was bubbled through a solution of Ethyl 5-bromo-2-phenylthiazole- 4-carboxylate (3.6 g, 11.5 mmol) and 2-(prop-2-ynyloxy)tetrahydro-2H-pyran (3.3 rnL, 23.1 mmol) in THF (30 mL). Dichlorobis(triphenylphosphine)palladium (II) (405 mg, 0.6 mmol), copper (I) iodide (55 mg, 0.3 mmol), and triethylamine (TEA) (8 mL, 57.7 mmol) were added and the reaction mixture was heated at 1000C for 30 min in a microwave reactor. The reaction mixture was poured into H2O and extracted with EtOAc. The combined organics were washed with brine, dried (MgSO4), and concentrated. The crude product was purified by MPLC eluting with pentane/EtOAc (0-50% gradient) to give ethyl 2-phenyl-5-(3-(tetrahydro-2H-pyran-2-yloxy)prop-l- ynyl)thiazole-4-carboxylate (3.8 g, 88 % yield)
  • 5
  • [ 6089-04-9 ]
  • [ 201230-82-2 ]
  • [ 103962-05-6 ]
  • [ 1202942-19-5 ]
YieldReaction ConditionsOperation in experiment
64% With copper(l) iodide; sodium hydrogencarbonate;bis(triphenylphosphine)palladium(II) dichloride; In tetrahydrofuran; water; at 20℃; for 48h; A solution of 2-(2-propynyloxy)tetrahydro-2/J-pyran (69) (0.758 g, 5.41 mmol), CuI (17 mg, 0.09 mmol) and PdCl2(PPh3)2 (0.158 g, 0.023 mmol) in THF (15 mL) was purged with N2. l-Iodo-4-(trifiuoromethoxy)benzene (70) (1.30 g, 4.51 mmol) in THF (10 mL) was added, followed by a solution of methylhydrazine sulfate (1.95 g, 13.5 mmol) and NaHCO3 (2.27 g, 27 mmol) in water (25 mL). The mixture was flushed with carbon monoxide and then stirred at room temperature for 2 days under one atmosphere of carbon monoxide. The resulting mixture was partitioned between CH2Cl2 and water, the CH2Cl2 fraction was dried, and the solvent was evaporated. Column chromatography of the residue on silica gel (eluting with CH2Cl2) gave 1 -methyl-5-[(tetrahydro-2//-pyran-2-yloxy)methyl]-3-[4-(trifluoromethoxy)phenyl]-lH-pyrazole (71) (1.034 g, 64%) as a brown solid: mp 40-42 0C; 1H NMR (CDCl3) δ 7.78 (d, J = 8.8 Hz, 2 H), 7.21 (d, J = 8.0 Hz, 2 H), 6.51 (s, 1 H), 4.75 (d, J = 12.8 Hz, 1 H), 4.69 (t, J= 3.3 Hz, 1 H), 4.57 (d, J- 12.8 Hz, 1 H), 3.94 (s, 3 H), 3.84-3.91 (m, 1 H), 3.53-3.60 (m, 1 H), 1.68-1.88 (m, 2 H), 1.50-1.66 (m, 4 H). APCI MS m/z 357 [M + H]+.
  • 6
  • [ 303-49-1 ]
  • [ 6089-04-9 ]
  • N,N-dimethyl-3-(3-(3-(tetrahydro-2H-pyran-2-yloxy)prop-1-yn-1-yl)-10,11-dihydro-5H-dibenzo[b,f]azepine-5-yl)propane-1-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% <strong>[303-49-1]Clomipramine</strong> 2 (0.503 g; 1.43 mmol; 1 equiv) was mixed with Cs2CO3 (1.13 g; 3.57 mmol; 2.5 equiv) and XPhos precatalyst PdG1 (0.0313 g; 0.0428 mmol; 3 mol %) in a glove box. To this anhydrous acetonitrile (4 mL) was added, and the reaction mixture was left with stirring, in the glove box for 25 min before THP protected propargyl alcohol (0.501 g; 3.57 mol; 2.5 equiv) was added. The reaction vessel was sealed, removed from the glove box, and then heated to 80 C for 20 h. After 20 h the reaction mixture was cooled to rt and quenched with saturated NaHCO3 (aq). The mixture was extracted with AcOEt, and the combined organic phases were dried over MgSO4, filtered and evaporated. The product was purified by column chromatography (first CH2Cl2/CH3OH 50:1 then CH2Cl2/CH3OH 20:1). Upon repeated column chromatography, the product was isolated as brown oil in 63% yield (0.375 g; 0.895 mmol). Rf (CH2Cl2/CH3OH 20:1) 0.45. 1H NMR (400 MHz, CDCl3) deltaH 7.16-7.02 (m, 4H), 6.99 (s, 2H), 6.94 (dt, 1H, J = 7.3, 1.1 Hz), 4.88 (t, 1H, J = 3.4 Hz) 4.46 (q, 2H, J = 15.7 Hz), 3.93-3.81 (m, 1H), 3.77 (t, 2H, J = 6.6 Hz), 3.61-3.50 (m, 1H), 3.12 (s, 4H), 2.60 (t, 2H, J = 5.6 Hz), 2.35 (s, 6H), 1.96-1.48 (m, 8H). 13C NMR (100 MHz, CDCl3) deltaC 147.9, 134.9, 134.4, 130.3, 129.7, 126.7, 125.9, 123.3, 123.2, 120.7, 120.4, 96.9, 86.0, 84.4, 62.1, 57.3, 54.9, 48.5, 44.9, 32.6, 31.8, 30.4, 25.5, 19.2 ppm. HRMS (ES+): Calcd for C27H34N2O2H: 419.2699; found 419.2699.
  • 7
  • [ 6089-04-9 ]
  • [ 128742-76-7 ]
  • C14H15NO2 [ No CAS ]
  • 8
  • [ 6089-04-9 ]
  • [ 1626-24-0 ]
  • C26H26GeO2 [ No CAS ]
 

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